LEPROSY BACILLUS,: FROM GENOTYPE TO PHENOTYPE

描述(改编自申请人的摘要)：本报告的目的 完全改版的重新提交是识别和实施 用于麻风和IS诊断和流行病学监测的新抗原 基于刚刚测序的连续麻风杆菌基因组，研究人员的 独一无二地接触到细菌，并在非凡的驱动下 流行率下降和上升趋同的流行病学难题 发病率。另一个假设驱动的推动力是，有缺陷的基因必须 将反映在截断的表型中，其定义还将 提供知识和工具，帮助解释麻风病的特点，如 作为专性的细胞内趋向性、特征性细胞嗜性和反应。S. 科尔(巴斯德研究所)将完成对基因组的分析和注释 并生成数据库，为两个实验室的工作提供手段 (L的巴斯德研究所；CSU)定义转录组，在 感染剂，以及通过克隆整个简化的蛋白质组 靶向基因和体内表达蛋白全序列的定义。 CSU将把分支杆菌的基因组和结构知识应用于 定义简化的次级基因产物(LepLAM；Lm；新的胞外基因 脂类；肽多聚糖等)。CSU、菲奥-克鲁兹(C.Pessolani)和延世 大学(S.N.Cho)将联合起来在豚鼠身上测试新产品的迟发型超敏反应 麻风患者PBMC对合适T细胞的应答 反应性和针对血清的抗体反应，以期推动 新的皮肤抗原倡议，并为早期提供新的血液检测 高危人群的诊断和识别。

DESCRIPTION (Adapted from the Applicant's Abstract): The purpose of this completely revamped resubmission is the identification and implementation of new antigens for the diagnosis and epidemiological monitoring of leprosy and is based on the just-sequenced contiguous M. leprae genome, on the investigators' singular access to the bacillus, and driven by the extraordinary epidemiological conundrum of a convergence of falling prevalence and rising incidence. The other hypothesis-driven thrust is that a defective genotype must be reflected in a truncated phenotype, the definition of which will also provide knowledge and tools to help explain the peculiarities of leprosy, such as obligate intracellularism, characteristic cell tropism and reactions. S. Cole (Institut Pasteur) will complete the analysis and annotation of the genome and generate databases to provide the means for a two-laboratory effort (L'Institut Pasteur; CSU) to define the transcriptome, polymorphism within the infectious agent, and the entire simplified proteome through cloning of targeted genes and definition of the full array of in vivo expressed proteins. CSU will apply the genome and the structural knowledge of mycobacteria to define the simplified secondary gene products (LepLAM; LM; new extracellular lipids; peptidoglycan; etc.). CSU, Fio-Cruz (C. Pessolani), and Yonsei University (S.-N. Cho) will combine to test new products in guinea pigs for DTH responses, against PBMC's of leprosy patients for appropriate T-cell reactivity, and against sera for antibody responses, with a view to advancing the new skin antigen initiative and providing new blood assays for early diagnosis and identification of a t risk populations.